This invention relates to medicament respiratory delivery devices for pulmonary, intranasal and buccal respiratory delivery of medicaments including an encapsulated medicament cartridge having a piercing element.
Inhalers and atomizers are now commonly used primarily to deliver various liquid medicaments via the patient""s or user""s nose or mouth. As used herein, xe2x80x9cmedicamentxe2x80x9d includes any powder or liquid medicament, drug or vaccine which may be administered from a respiratory delivery device through the user""s nose or mouth, sometimes referred to herein as a medicament respiratory delivery device. More recently, the prior art has proposed unit dose disposable powder medicament delivery devices, such as disclosed in U.S. Pat. No. 5,215,221, wherein a predetermined quantity or unit dose of a powder medicament is sealed in a reservoir formed between opposed thermoplastic sheets and expressed or delivered by application of manual force to a thermoformed blister which, upon actuation, breaks a burstable seal between the sheets at the entrance to the reservoir and fluidizes the powder medicament in the reservoir through a delivery tube. The delivery tube is cut prior to use.
There are several considerations affecting the design and efficacy of medicament respiratory delivery devices. First, it is important to ensure that a predetermined quantity or dose of medicament is consistently delivered to the user with each application. Second, because respiratory therapy often requires numerous applications, the cost of providing the dosage should also be considered. That is, it is desirable that the medicament respiratory delivery device consistently express substantially all of the medicament to the user and that the delivery device is not susceptible to user error in operation. Third, it is important that the medicament be properly disbursed or entrained in the conveying fluid. Further considerations include operating complexity, cost of the device, portability and size of the delivery device.
The embodiments of the medicament respiratory delivery devices and medicament cartridge of this invention provides a reproducible, high level of clearance of medicament or emitted dose from the cartridge upon actuation with modest gas pressure.
The medicament respiratory delivery device of this invention includes a housing having a chamber, an inlet communicating with the chamber, and an outlet preferably generally coaxially aligned with the inlet and a medicament cartridge located within the chamber. The medicament cartridge includes a body portion having opposed ends and a passage extending through the body portion through the opposed ends. In the most preferred embodiment, the passage is generally cylindrical, but may have other shapes including an hourglass shape. The passage includes the medicament, which may be a unit dose of a liquid or powder medicament, drug or vaccine as discussed further hereinbelow. One end of the passage is sealed with a pierceable closure which may be formed during molding of the cartridge and the opposed end of the cartridge passage opposite the outlet of the medicament delivery device is sealed with a burstable membrane, preferably comprising a thin sheet of polyolefin or a polyolefin blend or copolymer having a thickness between 0.3 and 1.5 mils and a burst pressure of between 1.2 and 10 atmospheres, more preferably less than 5 atmospheres and most preferably between 1.5 and 4 atmospheres. The term polyolefin is understood to mean a polymer containing olefin units such as, for example, ethylene, propylene or 1-butene units or any other alpha-olefin. Polyolefin as used herein includes polyethylene, polypropylene, ethylene-.alpha. olefin copolymer, wherein the alpha olefin having from 3 to 20, preferably 4 to 8 carbon atoms, polyolefin copolymers made by polymerizing olefins in the presence of a metallocene catalyst, ethylene-vinyl acetate copolymer, ethylene-ethyl acrylate copolymer, and ethylene-methyl acrylate copolymer. In particular, it is desirable to use polyethylene, such as low-density, linear-low-density, very-low-density, medium-density, or high-density polyethylene, or polypropylene, such as a polypropylene homopolymer, ethylene-propylene copolymer, or ethylene-propylene block copolymer. In the most preferred embodiment, the end of the cartridge at the outlet of the delivery device is convex or frustoconical surrounding the passage and a polymeric film is stretched taut over the convex surface and bonded or fused to the convex surface, thereby avoiding wrinkles or bulges in the burstable membrane which may adversely affect the consistency of the emitted dose of the delivery device.
The medicament respiratory delivery device of this invention further includes a piercing element movable to pierce the pierceable closure of the cartridge and a manually compressible pressure actuator which delivers fluid under pressure through the housing inlet upon piercing of the pierceable closure, thereby rupturing the burstable membrane and expressing the medicament in the passage entrained in fluid to the outlet of the delivery device. In the most preferred embodiment, the piercing element pierces the pierceable closure prior to delivery of sufficient pressure to the burstable membrane to rupture the membrane. In the preferred embodiment, the piercing element includes an actuator portion and a shaft portion having a piercing end and the cartridge includes an integral tubular portion coaxially aligned with the pierceable closure which receives the piercing end of the shaft and which guides the piercing end of the piercing element. In this embodiment, the actuator portion of the piercing element is located within the pressure actuator, such that actuation of the pressure actuator also moves the shaft portion of the piercing element to pierce the pierceable closure.
In the preferred embodiment of the medicament respiratory delivery device of this invention, the housing is comprised of two opposed thermoformed thermoplastic sheets bonded together, wherein the sheets have formed therebetween a central chamber, an inlet communicating with the chamber, a collapsible or compressible pressure actuator having an outlet communicating with the inlet to the chamber and an inlet opposite the inlet to the chamber preferably including a generally conical diffuser portion. The medicament cartridge is thereby encapsulated between the thermoformed thermoplastic bonded sheets forming the housing chamber. In the disclosed embodiment, the pressure actuator is bulb-shaped, preferably symmetrical with respect to the axis of the inlet and outlet of the chamber; however, the pressure actuator may also be a bellows-type pressure actuator either symmetrical with respect to the axis of the chamber inlet and outlet or extending from either of the thermoformed sheets. Where the pressure actuator is bulb-shaped or spherical, the acuator portion of the piercing element is bow-shaped having a concave arcuate portion generally conforming to the bulb-shape of the pressure actuator and a concave arcuate portion connected to or integral with the ends of the concave arcuate portion and the shaft portion is connected to the end of the concave portion, such that compression collapsing of the bulb-shaped pressure actuator collapses the actuator portion of the piercing element, driving the piercing end of the shaft through the pierceable closure of the capsule and deliver fluid under pressure to the cartridge passage, rupturing the burstable membrane and expressing entrained medicament through the outlet of the delivery device.
As set forth above, the medicament respiratory delivery device of this invention may be utilized to aerosolize any medicament, drug or vaccine, referred to herein generically as a medicament, including liquid, powder or even gaseous medicaments. For example, the cartridge may contain a unit dose of a liquid or powder medicament or the bulb may be filled with a liquid, such as a diluent or medicament, and the cartridge may be filled with a powder medicament, wherein the powder medicament is simultaneously reconstituted by a diluent, for example, and expressed by the medicament respiratory delivery device of this invention to the respiratory system of a user or patient.
The preferred embodiments of the medicament respiratory delivery device of this invention are particularly, but not exclusively, adapted for pulmonary, intranasal or buccal medicament delivery of a liquid or powder medicament, wherein the patient""s inspiratory flowrate is not the driving force behind the delivery of the medicament. In the most preferred embodiment, the burstable membrane is formed of a preferentially oriented polyolefin film, preferably a uniaxially oriented polyethylene film having a thickness of about 1 mil and having a burst pressure of less than 5 atmospheres. Polyolefin films can be oriented by drawing in one or both mutually perpendicular directions in the plane of the film to impart strength thereto using methods known in the art. Oriented polyolefin films include machine direction and transverse direction orientation. Oriented polyolefin films include uniaxially or biaxially oriented films, with uniaxially oriented films being preferred. Uniaxially-oriented films have properties to their advantage for use as the burstable membrane, including relatively high stiffness, as indicated by the tensile modulus in a particular direction, usually the machine direction, compared to the transverse direction. Properties of the oriented polyolefin film can be dependent to a certain degree on the particular process conditions under which the polyolefin film was manufactured. For example, a stiffer film with lower transverse burst pressure properties would result from an orientation process incorporating a larger machine direction orientation draw ratio. Thus, oriented polyolefins films can be tailored to provide an appropriate burst pressure property within a preferred film thickness range. However, the burstable film may also be formed from various polymers, including cast polyethylene and polyethylene copolymers and scored or embossed polypropylene, acetate or polycarbonate. The medicament respiratory delivery of this device consistently delivers a predetermined quantity or dose of medicament to the respiratory system, is relatively simple and inexpensive to manufacture, and preferably is disposable following use. Other advantages and meritorious features of the medicament respiratory delivery device of this invention will be more fully understood from the following description of the preferred embodiments, the claims and the appended drawings, a brief description of which follows.